Drug treatment corrects autism symptoms in mouse model

March 13, 2013

Autism results from abnormal cell communication. Testing a new theory, researchers at the University of California, San Diego School of Medicine have used a newly discovered function of an old drug to restore cell communications in a mouse model of autism, reversing symptoms of the devastating disorder.

The findings are published in the March 13, 2013 issue of the journal PLOS ONE.

"Our (cell danger) theory suggests that autism happens because cells get stuck in a defensive metabolic mode and fail to talk to each other normally, which can interfere with brain development and function," said Robert Naviaux, MD, PhD, professor of medicine and co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego. "We used a class of drugs that has been around for almost a century to treat other diseases to block the 'danger' signal in a mouse model, allowing cells to return to normal metabolism and restore cell communication."

"Of course, correcting abnormalities in a mouse is a long way from a cure for humans," said Naviaux, "but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year. This trial is still in the early stages of development. We think this approach – called antipurinergic therapy or APT – offers a fresh and exciting new path that could lead to development of a new class of drugs to treat autism."

Autism spectrum disorders (ASDs) are complex disorders defined by abnormalities in the development of language, social and repetitive behaviors. Hundreds of different genetic and environment factors are known to confer risk. In this study, nearly a dozen UC San Diego scientists from different disciplines collaborated to find a unifying mechanism that explains autism. Their work is the result of one of just three international "Trailblazer" awards given by the group Autism Speaks in 2011.

Describing a completely new theory for the origin and treatment of autism using APT, Naviaux and colleagues introduce the concept that a large majority of both genetic and environmental causes for autism act by producing a sustained cell danger response – the metabolic state underlying innate immunity and inflammation.

"When cells are exposed to classical forms of dangers, such as a virus, infection or toxic environmental substance, a defense mechanism is activated," Naviaux explained. "This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking."

Since mitochondria – the so-called "power plants" of the cell – play a central role in both infectious and non-infectious cellular stress, innate immunity and inflammation, Naviaux and colleagues searched for a signaling system in the body that was both linked to mitochondria and critical for innate immunity. They found it in extracellular nucleotides like adenosine triphosphate (ATP) and other mitokines – signaling molecules made by distressed mitochondria. These mitokines have separate metabolic functions outside of the cell where they bind to and regulate receptors present on every cell of the body. Fifteen types of purinergic receptors are known to be stimulated by these extracellular nucleotides, and the receptors are known to control a broad range of biological characteristics with relevance to autism.

The researchers tested suramin – a well-known inhibitor of purinergic signaling used medically for the treatment of African sleeping sickness since shortly after it was synthesized in 1916 – in mice. They found that this APT mediator corrected autism-like symptoms in the animal model, even if the treatment was started well after the onset of symptoms. The drug restored 17 types of multi-symptom abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination and normalizing mitochondrial metabolism.

"The striking effectiveness shown in this study using APT to 'reprogram' the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders," Naviaux said.

Related Stories

(Medical Xpress)—Results of a recent clinical study by researchers from Western and the University of Arkansas reveal the presence of a unique blood marker, which may further the understanding of possible gut linked environmental ...

A study led by Eric Courchesne, PhD, director of the Autism Center of Excellence at the University of California, San Diego School of Medicine has, for the first time, identified in young autism patients genetic mechanisms ...

Scientists affiliated with the UC Davis MIND Institute have discovered how a defective gene causes brain changes that lead to the atypical social behavior characteristic of autism. The research offers a potential target for ...

A study by researchers at the University of California, San Diego Autism Center of Excellence shows that brain overgrowth in boys with autism involves an abnormal, excess number of neurons in areas of the brain associated ...

A new study out today in the journal Cerebral Cortex challenges the hypothesis that nerve cells in the brains of individuals with Autism Spectrum Disorders do not reliably and consistently respond to external stimuli.

Autism spectrum disorder is caused by a variety of factors, both genetic and environmental. But a new study led by UCLA scientists provides further evidence that the brains of people with the disorder tend to have the same ...

A new study conducted by researchers at Marcus Autism Center, Children's Healthcare of Atlanta, and Emory University School of Medicine helps put to rest a longstanding controversy and question about children with autism ...

Treatments for autism spectrum disorders are varied and costly, and selecting the right one is crucial to long-term outcome. Yale University researchers report they can predict whether a preschool age child will respond to ...

Autism is an agonizing puzzle, a complex mixture of genetic and environmental factors. One piece of this puzzle that has emerged in recent years is a biochemical cascade called the mTOR pathway that regulates growth in the ...

Quite a large number of important scientists are thought to have or had autism (specifically Asperger's.) Einstein, for one, and who would want to "cure" him? Or the others?

I only speak for myself but life isn't always that great when you are socially debilitated. Watching other people communicate so effortlessly and carefree when the only topic that comes naturally to your mind is something like "human communication is so interesting" or "I wonder what material they use in those football pads". It's not all fun, games, and Nobel's. ;-)

"Of course, correcting abnormalities in a mouse is a long way from a cure for humans," said Naviaux, "but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year.

I don't get it. They've made a groundbreaking discovery. Why can't they just put the fast forward on this research and start the human trials now? Why do these things always have to take an insane amount of time? It's exactly the same thing with new cancer drugs.

because they might have unintended side effects, would you risk your child on such a trial or someone else's? Would you want pressure on autistic kids to take this drug, when actually it might be quite interesting to know what material is in those football pads and to be honest who cares about celebrity lifestyles and all those other neurotypical obsessions? Who says that is more interesting than other stuff? And yes I know autism is a spectrum.

What about diet? My son has made remarkable progress with the Specific Carbohydrate diet (SCD) and a battery of supplements. I'm curious as to whether suramin counters the effects of "partially digested" gluten and casein in the diet? The plan behind the SCD is to allow the digestive system to heal, and perhaps eventually allow the person to consume the offending proteins... When we first removed gluten and casein (we started with the GFCF diet) from our son's diet, he emerged from a completely self-isolated non-verbal state of being to smiling within a week, and now the only vestiges of ASD he exhibits are speech impediments. It has been a arduous journey, but the reward is priceless.

because they might have unintended side effects, would you risk your child on such a trial or someone else's? Would you want pressure on autistic kids to take this drug,

I don't have kids. But I do know that if I had a child that was debilitated or non-verbal, I would be hoping for something to help him/her now, as opposed to 50 years into the future when it's not going to be of much use anyway. Sure, there are those on the higher functioning end of the spectrum, who consider it part of their identity and sometimes have no problem with it. But there are also those on the lower end of the spectrum, requiring constant, personalized care.

@claudius, i dont think so. Neanderthals were far less creative than homosapiens(us).One of the reasons we out manouvered neanderthals in taking over the world is because of our comparitively advanced tools made possible by creativity. And autism and creativity are far closely related than autism and non creativity.

Quite a large number of important scientists are thought to have or had autism (specifically Asperger's.) Einstein, for one, and who would want to "cure" him? Or the others?

No, only a few people think so, the evidence for historical figures having had autism is very thin and it's too weak to draw the kind of conclusions you are drawing in my ever so humble opinion. I'm not a health expert, but these people were never examined and all you have to go on are speculation based on.. what exactly?

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.